Pressure-overload hypertrophy is unabated in mice devoid of AT1A receptors

1998 ◽  
Vol 274 (3) ◽  
pp. H868-H873 ◽  
Author(s):  
Masayoshi Hamawaki ◽  
Thomas M. Coffman ◽  
Andrew Lashus ◽  
Masaaki Koide ◽  
Michael R. Zile ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Knockout Mice ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Wild Type ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Hypertrophic Response

Mechanisms controlling cardiac growth are under intense investigation. Among these, the renin-angiotensin system has received great interest. In the current study, we tested the hypothesis that the renin-angiotensin system was not an obligate factor in cardiac hypertrophy. We examined the left ventricular hypertrophic response to a pressure overload in mice devoid of the AT1A receptor, the putative major effector of the growth response of the renin-angiotensin system. Aortic banding produced similar transband gradients in wild-type and AT1A knockout mice. The left ventricular mass-to-body weight ratio increased from 3.44 ± 0.08 to 5.62 ± 0.25 in wild-type ascending aortic-banded mice. The response in the knockout mice was not different (from 2.97 ± 0.13 to 5.24 ± 0.37). We conclude that the magnitude of cardiac hypertrophy is not affected by the absence of the AT1A receptor and its signaling pathway and that this component of the renin-angiotensin system is not necessary in cardiac hypertrophy.

Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats

1990 ◽  
Vol 259 (2) ◽  
pp. H324-H332 ◽  
Author(s):  
K. M. Baker ◽  
M. I. Chernin ◽  
S. K. Wixson ◽  
J. F. Aceto
Keyword(s):  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Abdominal Aorta ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Angiotensin I ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Nuclease Mapping

We have recently shown that the octapeptide angiotensin II is a potent stimulus of protein synthesis and growth in cultured cardiomyocytes. The present study was performed to determine if the renin-angiotensin system was involved in regulating cardiac cell growth in vivo. The pressure-overload cardiac hypertrophy model that develops in abdominal aorta-constricted rats was studied. At 7 and 15 days after abdominal aorta constriction, rats developed significant left ventricular hypertrophy. The increase in left ventricular mass was completely prevented in animals fed the angiotensin-converting enzyme inhibitor, enalapril maleate (0.2 mg/ml) in their drinking water. Cardiac afterload was the same in both groups of animals in that carotid artery pressures were not different in conscious awake aortic-constricted animals receiving and not receiving enalapril. These data suggest a direct growth effect of angiotensin II on the left ventricle and indicate a role for the renin-angiotensin system in the cardiac hypertrophy that develops in response to pressure overload. The presence and chamber localization of angiotensinogen mRNA was determined using Northern hybridization and S1 nuclease mapping analysis. Angiotensinogen mRNA, as determined by dot-blot hybridization analysis, was significantly increased in hypertrophied left ventricles at both 7 and 15 days after the surgery, when compared with sham-operated controls. The activity of the circulating renin-angiotensin system, as indexed by plasma renin activity was increased at 1 day following surgery [6.0 +/- 2.0 ng.ml-1.h-1 angiotensin I (control) vs. 41.8 +/- 10.9 ng.ml-1.h-1 angiotensin I (experimental)], but returned to control values by day 3 postoperatively.(ABSTRACT TRUNCATED AT 250 WORDS)

Active renin and angiotensinogen in cardiac interstitial fluid after myocardial infarction

1999 ◽  
Vol 276 (6) ◽  
pp. H1818-H1826 ◽  
Author(s):  
Alan T. Hirsch ◽  
John A. Opsahl ◽  
Mary M. Lunzer ◽  
Stephen A. Katz
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Hypertrophy ◽  
Infarct Size ◽  
Interstitial Fluid ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Active Renin

The renin-angiotensin system promotes cardiac hypertrophy after myocardial infarction. The purpose of this study was to measure renin and angiotensinogen in plasma and myocardium 10 days after myocardial infarction. Infarction involving 45 ± 4% of left ventricular circumference with accompanying hypertrophy was induced in rats ( n = 14). Plasma and myocardial renin were increased after infarction compared with sham controls ( n = 8) (27.4 ± 3.2 vs. 7.5 ± 1.8 ng ANG I ⋅ ml plasma ⋅ h−1, P < 0.0002; and 8.8 ± 1.6 vs. 2.5 ± 0.1 ng ANG I ⋅ g myocardium−1 ⋅ h−1, P < 0.008, respectively). After infarction, myocardial renin was correlated with infarct size ( r = 0.62, P < 0.02) and plasma renin ( r = 0.55, P < 0.04). Plasma angiotensinogen decreased in infarct animals, but myocardial angiotensinogen was not different from shams (1.1 ± 0.08 vs. 2.03 ± 0.06 nM/ml plasma, P < 0.002; and 0.081 ± 0.008 vs. 0.070 ± 0.004 nM/g myocardium, respectively). In conclusion, myocardial renin increased after infarction in proportion to plasma renin and infarct size, and myocardial angiotensinogen was maintained after infarction despite decreased plasma angiotensinogen and increased levels of myocardial renin.

scholarly journals Role of the renin-angiotensin system in cardiac hypertrophy induced in rats by hyperthyroidism

1997 ◽  
Vol 273 (2) ◽  
pp. H593-H599 ◽  
Author(s):  
H. Kobori ◽  
A. Ichihara ◽  
H. Suzuki ◽  
T. Takenaka ◽  
Y. Miyashita ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Renin Angiotensin System ◽  
Sympathetic Denervation ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Sympathetic Nervous

This study was conducted to examine whether the renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy without involving the sympathetic nervous system. Sprague-Dawley rats were divided into control-innervated, control-denervated, hyperthyroid-innervated, and hyperthyroid-denervated groups using intraperitoneal injections of thyroxine and 6-hydroxydopamine. After 8 wk, the heart-to-body weight ratio increased in hyperthyroid groups (63%), and this increase was only partially inhibited by sympathetic denervation. Radioimmunoassays and reverse transcription-polymerase chain reaction revealed increased cardiac levels of renin (33%) and angiotensin II (53%) and enhanced cardiac expression of renin mRNA (225%) in the hyperthyroid groups. These increases were unaffected by sympathetic denervation or 24-h bilateral nephrectomy. In addition, losartan and nicardipine decreased systolic blood pressure to the same extent, but only losartan caused regression of thyroxine-induced cardiac hypertrophy. These results suggest that thyroid hormone activates the cardiac renin-angiotensin system without involving the sympathetic nervous system or the circulating renin-angiotensin system; the activated renin-angiotensin system contributes to cardiac hypertrophy in hyperthyroidism.

Renin-angiotensin system and sympathetic nervous system in cardiac pressure-overload hypertrophy

2000 ◽  
Vol 279 (6) ◽  
pp. H2797-H2806 ◽  
Author(s):  
Wendell S. Akers ◽  
Andrew Cross ◽  
Robert Speth ◽  
Linda P. Dwoskin ◽  
Lisa A. Cassis
Keyword(s):  
Left Ventricle ◽  
Adrenergic Receptor ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Receptor Density ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Sympathetic Nervous

Angiotensin II and norepinephrine (NE) have been implicated in the neurohumoral response to pressure overload and the development of left ventricular hypertrophy. The purpose of this study was to determine the temporal sequence for activation of the renin-angiotensin and sympathetic nervous systems in the rat after 3–60 days of pressure overload induced by aortic constriction. Initially on pressure overload, there was transient activation of the systemic renin-angiotensin system coinciding with the appearance of left ventricular hypertrophy ( day 3). At day 10, there was a marked increase in AT1 receptor density in the left ventricle, increased plasma NE concentration, and elevated cardiac epinephrine content. Moreover, the inotropic response to isoproterenol was reduced in the isolated, perfused heart at 10 days of pressure overload. The affinity of the β2-adrenergic receptor in the left ventricle was decreased at 60 days. Despite these alterations, there was no decline in resting left ventricular function, β-adrenergic receptor density, or the relative distribution of β1- and β2-receptor sites in the left ventricle over 60 days of pressure overload. Thus activation of the renin-angiotensin system is an early response to pressure overload and may contribute to the initial development of cardiac hypertrophy and sympathetic activation in the compensated heart.

Role of the renin-angiotensin system in the development of thyroxine-induced hypertension

1997 ◽  
Vol 136 (6) ◽  
pp. 656-660 ◽  
Author(s):  
Cipriano Garcia del Rio ◽  
María Rosario R Moreno ◽  
Antonio Osuna ◽  
Juan de Dios Luna ◽  
Joaquín García-Estañ ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Tap Water ◽  
Weight Ratio ◽  
Renin Angiotensin System ◽  
Control Group ◽  
Angiotensin System ◽  
Renin Angiotensin

Abstract Objective: We evaluated the influence of chronic blockade of the renin-angiotensin system on hypertension induced by long-term thyroxine (T4) administration. To this end, we determined the effects of chronic treatment with captopril on blood pressure, cardiac hypertrophy and other renal and metabolic variables of hypertensive hyperthyroid rats. Methods: T4 was administered s.c. at 0·38 μmol/kg per day and captopril was given in the drinking water (1·38 mmol/l). Both treatments were maintained for 6 weeks. Control rats received tap water. After the treatment period, the rats were placed in metabolic cages. Later, blood pressure was measured in conscious rats by intra-arterial determination. Results: T4-treated rats showed an increased mean arterial pressure (MAP) whereas, in rats treated with T4 plus captopril, MAP was similar to that of the control group. Captopril did not affect the increased heart rate or ventricular weight/body weight ratio of hyperthyroid rats, but it improved the reduced creatinine clearance of these animals. Conclusions: The elevation in blood pressure produced by long-term T4 administration was prevented by chronic blockade of the renin-angiotensin system. Captopril improved the renal function of hyperthyroid rats, but did not affect the relative cardiac hypertrophy of these animals. European Journal of Endocrinology 136 656–660

Angiotensin receptor 1 blockade does not prevent physiological cardiac hypertrophy in the adult rat

1996 ◽  
Vol 81 (2) ◽  
pp. 816-821 ◽  
Author(s):  
D. L. Geenen ◽  
A. Malhotra ◽  
P. M. Buttrick
Keyword(s):  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Heart Weight ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Hypertrophic Response ◽  
Adult Rat ◽  
At1 Antagonist ◽  
Physiological Cardiac Hypertrophy

The renin-angiotensin system has been implicated in the hypertrophic adaptation of the heart to exogenous pathological loads, such as hypertension and aortic stenosis; however, the role of this hormonal system in the cardiac adaptations to physiological loads, such as chronic exercise conditioning, has not been established. We therefore studied the effect of angiotensin receptor 1 (AT1) blockade on the chronic cardiac responses of rats subjected to an 8-wk swimming program. Compared with matched sedentary controls, untreated swimmers increased their left ventricular weights by 13%, and swimmers treated with the AT1 antagonist L-158809 increased their left ventricular weights by 11% (both P < 0.05 vs. sedentary controls). The incorporation of labeled amino acids into the heart at the time of death was unchanged in all groups, and therefore the increase in heart weight in both swim-conditioned groups appeared to reflect a decrease in the rate of protein degradation in the heart. Hearts from both swim-conditioned groups manifested an increase in the V1-predominant myosin isoform pattern but not an increase in atrial natriuretic factor mRNA expression or protein kinase C translocation. The fact that these patterns of adaptation are preserved in exercised conditioned animals treated with an AT1 antagonist suggests that the chronic hypertrophic response of the heart to physiological loads is not influenced by the renin-angiotensin system.

Increased natriuretic peptide receptor A and C gene expression in rats with pressure-overload cardiac hypertrophy

2006 ◽  
Vol 290 (4) ◽  
pp. H1635-H1641 ◽  
Author(s):  
Tue E. H. Christoffersen ◽  
Mark Aplin ◽  
Claes C. Strom ◽  
Soren P. Sheikh ◽  
Ole Skott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Left Ventricle ◽  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Pressure Overload ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Natriuretic Peptide Receptor ◽  
Angiotensin System ◽  
Peptide Receptor

Both atrial (ANP) and brain (BNP) natriuretic peptide affect development of cardiac hypertrophy and fibrosis via binding to natriuretic peptide receptor (NPR)-A in the heart. A putative clearance receptor, NPR-C, is believed to regulate cardiac levels of ANP and BNP. The renin-angiotensin system also affects cardiac hypertrophy and fibrosis. In this study we examined the expression of genes for the NPRs in rats with pressure-overload cardiac hypertrophy. The ANG II type 1 receptor was blocked with losartan (10 mg·kg−1·day−1) to investigate a possible role of the renin-angiotensin system in regulation of natriuretic peptide and NPR gene expression. The ascending aorta was banded in 84 rats during Hypnorm/Dormicum-isoflurane anesthesia; after 4 wk the rats were randomized to treatment with losartan or placebo. The left ventricle of the heart was removed 1, 2, or 4 wk later. Aortic banding increased left ventricular expression of NPR-A and NPR-C mRNA by 110% ( P < 0.001) and 520% ( P < 0.01), respectively, after 8 wk; as expected, it also increased the expression of ANP and BNP mRNAs. Losartan induced a slight reduction of left ventricular weight but did not affect the expression of mRNAs for the natriuretic peptides or their receptors. Although increased gene expression does not necessarily convey a higher concentration of the protein, the data suggest that pressure overload is accompanied by upregulation of not only ANP and BNP but also their receptors NPR-A and NPR-C in the left ventricle.

Isoproterenol-induced cardiac hypertrophy: role of circulatory versus cardiac renin-angiotensin system

2001 ◽  
Vol 281 (6) ◽  
pp. H2410-H2416 ◽  
Author(s):  
Frans H. H. Leenen ◽  
Roselyn White ◽  
Baoxue Yuan
Keyword(s):  
Cardiac Hypertrophy ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Male Wistar Rats ◽  
Β Receptor

To assess the possible contribution of the circulatory and cardiac renin-angiotensin system (RAS) to the cardiac hypertrophy induced by a β-agonist, the present study evaluated the effects of isoproterenol, alone or combined with an angiotensin I-converting enzyme inhibitor or AT1 receptor blocker, on plasma and LV renin activity, ANG I, and ANG II, as well as left ventricular (LV) and right ventricular (RV) weight. Male Wistar rats received isoproterenol by osmotic minipump subcutaneously and quinapril or losartan once daily by gavage. Plasma and LV ANGs were measured by radioimmunoassay after separation by HPLC. Isoproterenol alone decreased blood pressure, more markedly when combined with losartan or quinapril. Isoproterenol significantly increased LV and RV weight and total collagen. Neither losartan nor quinapril inhibited the increases in LV or RV weight. Losartan prevented the increase in RV collagen but enhanced the increase in LV collagen. Isoproterenol increased plasma renin, ANG I, and ANG II three- to fourfold. Isoproterenol combined with losartan or quinapril, caused marked further increases except for a significant decrease in plasma ANG II with quinapril. Isoproterenol alone did not increase LV ANG II and, combined with losartan or quinapril, actually decreased LV ANG II. These results indicate that isoproterenol-induced cardiac hypertrophy is associated with clear increases in plasma ANG II, but not in LV ANG II. Both losartan and quinapril lower LV ANG II below control levels, but do not prevent the isoproterenol-induced cardiac hypertrophy. These findings do not support a role for the circulatory or cardiac RAS in the cardiac trophic responses to β-receptor stimulation.

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